Abstract

To study the socio economical and clinico radiological profile of 474 diagnosed MDR TB cases who came for the initiation of MDR TB regimen in DRTB center of R.D.Gardi Medical college, Ujjain

This is a retrospective and prospective observational study for a total period of three years from October 2013
to September 2016. The patients were evaluated clinically, radiologically and were investigated thoroughly according to PMDT
guidelines and then were started on MDR TB treatment. The study was conducted at drug resistance tuberculosis center (DR-TB)
managed by department of Pulmonary Medicine.

474 cases were included in the study and we found that patients were in the age range of 10-84 years, maximum
patients were in age group of 30 to 39 years, and mean age was 38 yrs. Male to female ratio was 2.73 to 1, most of the patients
in the study were from rural area i.e. 61.6%. Illiteracy was found in 339 (71.5%) cases and out of these 339, 165 patients (48.6%)
were defaulter, 101(29.8%) are cases of relapse, 39(11.5%) were failure, 34(10.02%) of new cases. Maximum numbers of patient
were in lower class accounting 63.7% and upper lower class 31.6%, lower middle class only 4.5%. Study also showed mean
BMI was 14.9 kg/m2 (range 5.7-25.4 kg/m2), 88.6% of patients were undernourished with BMI less then 18.5kg/m2 .The most
common symptoms was cough seen in 96%, followed by fever 67.5%, Dyspnea 52.7%, Anorexia 26.2%, chest pain in 19.8% and
least common was haemoptysis seen in 7.6% of patient. Common co-morbidities with MDR-TB found was anemia in 176 out
of 474 (i.e.37.1%), 123(25.9%) COPD. Radiological severity showed 219(46.2%) moderate lesion, 139 (29.3%) mild, 107(22.6%)
extensive lesion and 9(1.9%) normal, 312(65.8%) of patient are non-cavitory and 162 (34.2%) are cavitory in which 99 (20.9%)
were unilateral and 63(13.3%) are bilateral cavitory lesion. Defaulter are most common accounting of 218(46.0%), relapse139
(29.3%) and failure 68 (14.3%), new 48 (10.2%), most of them had taken more than one episode of ATT (72.8%). Most common
source of ATT taken by patient is RNTCP it accounts 424 (89.5%) and 46 (9.7%) from private. 181 out of 474 (38.2%) cases delayed
the treatment for 1-7 days, 82 out of 474 (17.3%) cases delayed treatment for 8-10 days, 96 out of 474 (20.3%) cases delayed
treatment for 11-19 days and 115 out of 474 delayed the treatment for more than 19 days. 95 out of 474 cases i.e. 20.1% cases
come from more than 150 km away from their residing area for the initiation of treatment.

The epidemiological picture of TB showed that males were predominant in our study however female were more
affected in younger age group compared to male. More than 51% of the cases were in productive age group which affects
the socioeconomic condition of family and society. More than 2/3 of patients were from lower socioeconomic group with low
BMI. Therefore improving nutrition and immunity can play an important role. 2.3% of the cases were HIV reactive and were on
ART. Co-morbidities like COPD and Diabetes were seen in our study which were statistically significant and had impact on the
treatment outcome of results. Significant delay in initiation of MDR-TB regimen from date of DST was seen in 24.3% cases which
is matter of concern. Most of the patients had taken ATT from RNTCP in which Defaulter and relapse was major contributor of
MDR-TB suspect in our study and patient taking ATT privately were less. Large number of cases which resides more than 150
kilometers from DRTB center initiated the drug after a gap of more than 19 days from the date of DST.

Introduction

Tuberculosis now ranks alongside
Human Immunodeficiency Virus
(HIV) as a leading cause of death
worldwide.1 Tuberculosis (TB) kills
more adults in India than any other
infectious disease. In India every day

More than 6000 develop tubercular
disease.

More than 600 people die of
tuberculosis (i.e. 2 death every 5
min).1

Table 1: Co-morbidities and associated
conditions with MDR-TB

associated tuberculosis occurred in
2014 and 31000 estimated number of patients died among them.1 A major
obstacle to tuberculosis control is the
emergence of mycobacterium resistance
to antitubercular chemotherapy.2 Multi
drug resistant tuberculosis is caused
by strains of Mycobacterium tuberculosis
that are resistant in-vitro to isoniazid
and rifampicin with or without other
anti-tubercular drugs based on drug
sensitivity test results from a Revised
National Tuberculosis Control Program
certified culture and drugs sensitivity
tests laboratory. The outcome results
of multi drug resistant tuberculosis
patients remain suboptimal.

Material and Methods

This is a retrospective and
prospective observational study for
a total period of three years from
October 2013 to September 2016. The
study was conducted at drug resistance
tuberculosis center (DR-TB) managed
by department of Pulmonary Medicine.
Our study was conducted in six districts
(Neemuch, Mandsaur, Dewas, Ratlam,
Shajapur, Ujjain) of western Madhya
Pradesh linked to DR-TB center of
Ujjain with population of 86,84,807
people (census 2011).

Exclusion criteria: Those cases were
not included who were started on MDR
TB regimen at the periphery and did not
reported to DRTB center.

Procedure planned: All the multidrug
resistance tuberculosis (MDR-TB)
cases which were diagnosed at drug resistance tuberculosis (DR-TB) center
of R.D. Gardi Medical College or
referred from other places for initiation
of second line drugs underwent an
initial evaluation of the patient was
done which includes:

Step 1

Demographic variables of patient
which includes age, sex, education
level.

Detailed history of patient which
include history of presenting
illness, past history, personal
history and family history

General examination of the patient
including vitals, height and weight
Oxygen saturation of patient
(SpO2) by pulse oximetry.

Step 3

Collection of data and analysis

Descriptive data was collected and
studied accordingly.

Significant statistical test were
applied.

Observations and Results

A total of 474 MDR-TB patients were
included in the study. The mean, mode,
and median age are 38, 40, 36 year
respectively and range is 10-84 year.
Standard deviation (SD) is 13.4 year.
The total of more than 51% cases was in
the age group between 20-49 years i.e.
in the productive age group with Male:
Female ratio equals to 2.73: 1 showing
male were predominant. Female were
more in younger age group compared
to male with chi-square value 44.38 and
p value is 0.00. study shows that most of
patient belongs to rural area i.e. 61.6% with illiteracy seen in 71.5% of cases
followed by primary school education
in 19.4% cases, higher secondary
education in 7% cases and graduate
2.10% cases. Maximum numbers of
patient were in lower class accounting
63.7% and upper lower class 31.6%,
lower middle class only 4.5%.

Mean body mass index (BMI) was
14.9 kg/m2,(range 5.7 – 25.4 kg/m2),
maximum cases were undernourished
with BMI less than 18.5 kg/m2 in which
72.2% were severely undernourished
had BMI less than 16 kg/m2 followed
by (8.6%) with moderate thinness and
(7.8%) were mild thinness, a total of
(11.2%) of patients had normal BMI
and only one patient was overweight.

Smoking history was found to be
in 168 (35.4%) of total patients with 91
patients (19.2%) with alcohol history
while 81 patient consumed both alcohol
and smoking. Most common symptoms
was cough seen in 96%, followed by
fever 67.5%, Shortness of breath 52.7%,
anorexia 26.2%, chest pain in 19.8% and
least common was haemoptysis seen in
only 7.6% of patients.

The occupational profile of patients
revealed that a majority of them were
from labour class (36.3%) and farmer
(31.2%) followed by housewife (15.2%),
students (9.1%) and rest (8.2%) are
driver, salesman, watchman, constable,
electrician, LIC agent, shopkeeper etc.
In our study we found that 11(2.3%)
cases out of 474 were HIV positive and
were on ART.

Most commonsite is lung
parenchyma seen in 464 (97.9%) cases,
and only 10 (2.1%) extra-pulmonary cases were found. A total of 6.8% (32
out of 474) cases had history of contact
with patients of tuberculosis cases were found. A total of 6.8% (32
out of 474) cases had history of contact
with patients of tuberculosis

Radiological severity showed 219
(46.2%) cases with moderate, 139 (29.3%)
with mild, 107 (22.6%) extensive lesion
and 9 (1.9%) normal with 312 (65.8%)
cases with non-cavitory lesion and 162
(34.2%) cases with cavitory lesion in
which 99 (20.9%) were unilateral and
63(13.3%) are bilateral cavitory lesion.
Most of the cases 345 i.e. 72.8% took
ATT for more than one episode and
only 86 i.e. 16.9% took single episode
of ATT while 49 i.e. 10.3% cases had
no history of ATT prior to initiation
of MDR-TB drugs. Regarding ATT
taken by the patient prior to MDR-TB
they were categorized as defaulter
are most common accounting of 218
(46.0%), relapse 139 (29.3%) and failure
68 (14.3%), new 48 (10.2%). Cross
tabulation was done which showed
most of the patient are illiterate that
is 339 (71.5%) and out of these 339,
165 patients (48.6%) were defaulter,
101 (29.8%) are cases of relapse, 39
(11.5%) were failure, 34 (10.02%) of
new cases. Cases belonging to lower
socioeconomic defaulted on treatment
more often (Chi-square= 16.06 and p
value 0.01). In our study, most common
source of ATT taken by patient is from
RNTCP and it accounts 424 (89.5%)
cases and 46 (9.7%) cases took treatment
from private sources.

181 out of 474 (38.2%) cases delayed
the treatment for 1-7 days, 82 out of
474 (17.3%) cases delayed treatment for
8-10 days, 96 out of 474 (20.3%) cases
delayed treatment for 11-19 days and
115 out of 474 delayed the treatment for
more than 19 days. 95 out of 474 cases
i.e. 20.1% cases come from more than
150 km away from their residing area
for the initiation of treatment.

Cross tabulation was done between
delay in treatment start and distance of
patient from DRTB center (Chi-square=
11.557 and p value = 0.009) Concluding
that person residing far from DRTB
center initiated the drug after a gap
of more than 19 days (26.3%). Logistic
regression were applied and we found
that chances of mortality in MDR-TB patients having COPD is 0.486 times
higher as compare to non - COPD
patients and chances of mortality in
MDR-TB patients having diabetes is
0.325 times higher as compare to non
diabetic patients.

Discussion

Our study at Drug Resistance
(DR-TB) centre mostly covered a rural
population. Most of the patient in our
study were from a low socioeconomic,
background with low education level
and were nutritionally challenged.

The study gave special attention to
spatiotemporal pattern of the MDR-TB
patients so that the spread of the cases
can be analyzed along with the co
morbidities associated with cases so
that any factor could be found out that
may prevent spread of the disease,
resolving of these factor may also help
in better compliance of treatment.

In the present study majority of the
MDR-TB, cases (more than 51%) were
in the productive age group (20-49
years); mean age was 38 years. In a
retrospective study done in a TB unit
in Mumbai, by Dholakia and Shah3
noted, that majority of the cases (67.6%)
were in the age group 15-35 years with
a mean age of 31years. Udwadia and
Moharil, Sharma et al4,5 reported that
prevalence of younger age group among
MDR-TB patients with the mean age of
their study groups being 29.7 years
and 33.25 years respectively. As most
of our patients are from economically
productive age group and some are the
sole source of income for the family, the
illness will impose an economic burden
at all level in society and for the nation.
Financial and nutritional support of
these patients now being planned by
government and NGO is a useful step
in the direction.

Males constitute 73.2% (347 cases)
of patients included in this study
while females were 26.8% (127 cases)
with male to female ratio is 2.73 to
1. However, studies by Udwadia et
al4reported female were predominant
Our study almost coincide with Singh et
al,6 Ibrahim et al,7 Songhua et al8 but did
not coincide with Udwadia et al4 which is
based on urban area and well educated
class of society. Majority of our cases
were male (73.2%) male predominance
among MDR-TB cases has been also
reported by other authors.9 Mean age
of females (31.66±12.63) was less than that of males (40.33±13.03), which is
statistically significant (t=6.46, p=.000).
Poulomi et al10 also reported that mean
age of female (28.59±12.50) was less
than male (34.97±12.84).

Ibrahim et al7 Males were significantly
older than females [38.99 ± 12.01 versus
34.52± 14.36 years, (P < 0.05)]. The T-test
is 6.46. The p-value is 0.000. The result
is significant at p < 0.05. Conclude that
young age group female more affected
than male.

Most of patient belongs to rural
area i.e. 61% of total and rest 31%
resides in the urban area. Results were
statistically significant (Z-score is 6.755
and p value is < 0.05). Study, coincide
with Ibrahim et al7 which showed that
81.5% patients were lived in rural area
and 18.5% of patients were in urban.
K.Aid et al11 also reported that most of
the patients were from rural area.

Most of the patients were illiterate
71.5% followed by primary school
19.4% , higher secondary 7% and
graduate 2.1%. Khurram et al12 reported
that 18 (60%) patients were illiterate
in his study, Dholakia et al3 only
14.17% of patients are illiterate did not
coincide with our study, because this
is urban based study. Songhua, et al8
the education levels of the cases were
as follows: 57 (58.2%) had finished
elementary school or graduated from
middle school and 17 (17.3%) had
never been to school or did not finish
elementary school.

Based on Kuppuswami scale13 most
of the patients in our study 302(63.7%),
belongs to lower class followed by
upper lower class 150 (31.6%) and lower
middle 22(4.5%) class respectively.
Study coincide with Atre et al14 study
shows most of patient come under
unemployed and unskilled worker.
The long duration of debilitation
further pushes the family to economic
hardship.

420 patients (88.6%) were
undernourished with BMI less than18.5
kg/m2 in which 72.2% were severely
undernourished had BMI less than 16
kg/m2 followed by 8.6% with moderate
thinness and 7.8% were mild thinness.
A total of 11.2% of patients had
normal BMI and only one patient was
overweight with Mean body mass
index (BMI) of 14.9kg/m2, (range 5.7-
25.4).

The mean BMI of present study
was less than other studies because this is rural based study and majority
of our patients belonged to lower
socioeconomic class with poor
nutritional status (Chi-square =86.96
and p value =0.000).

Regarding the associated addiction,
it was seen that 35.4% of the included
patients were smokers . Ibrahim
et al7 shows 42.5% of the studied
patients were tobacco smokers with
significantly higher prevalence among
males [56.8% of males verses 1.9%
of females were tobacco smokers
(p< 0.001)]. Khurram et al12 reported
Eighteen (60%) patients were smokers,
K.Aid et al11 who reported 74% were
smokers which might be because of
small sample size i.e.29 in which males
were predominant. In present study
cough was most common symptoms
seen in 455 (i.e. 96%) of patient. Other
studies in India to be shows that most
common symptoms was cough by
Udwadia et al,4 Mukherjee et al[10]etc.

The occupational profile of our
patients revealed that a majority of
them were labour 36.3% followed by
farmer 31.2% and housewife 15.2%.
Mukherjee et al10 reveals most common
group was household worker. Wei-bin
et al shows unskilled worker was most
commonly affected followed by farmer

Our study showed that 39 out of
474 cases suffered from Diabetes and
study coincides with studies done by
Singh et al6 and K. Aid et al.11 Patients
were managed with insulin and in
some cases oral hypoglycemic agent
for the control of blood sugar. Suitable
advices on diet and disease control
were given. Kapadia et al17 did not
reported any patient with thyroid
abnormality, in our study out of 27
cases of hypothyroidism 15 were male
and 12 were female (chi-square 6.37 and p value 0.04 i.e. < 0.05).

Assessment based on radiological
severity wad done and we found that
219(46.2%) had moderate lesion, 139
(29.3%) mild, 107(22.6%) extensive
lesion and 9(1.9%) normal which were
cases of extra pulmonary tuberculosis,
endobronchial TB, laryngeal TB. Our
study showed that 312 (65.8%) of
patient had non-cavitory lesion and 162
(34.2%) cases had cavitory lesion out of
which 99 (20.9%) were unilateral and
63 (13.3%) are bilateral cavitory lesion.
K.Aid et al11 study do not coincide
with our study shows 62 patients
(52.1%) as minimal lesions, 53 patients
(44.5%) as moderately advanced and 4
patients as far advanced lesions (3.4%).
Ebru et al19 shows 51 (79.7%) patients
had cavity and 34 (53.1%) patients
had extensive disease whereas, 30
(46.9%) patients had limited disease.
This study did not coincide with
our study. Udwadia et al4 shows, 33
(42.3%) patients had unilateral disease
while 42 (53.8%) had bilateral and
advanced disease. Findings of our
study do not coincide with Fawzy et
al,20 where minimal lesions were the
most common presentation among
his patients whereas in our study
moderate presentation was dominant
andAbdelazim et al who revealed that
58% of patients had far advanced lesion
in chest X-ray followed by minimal
lesion in chest X-ray 26%. Dholakia
et al3 shows a total of 20 of the 25 PTB
cases had cavitary lesions, 13 single
and 7 more than one cavity; 14 cavities
were unilateral and 6 bilateral. A total
of 20 of the 25 PTB cases had moderate
to extensive lesions on x-rays.

Majority of cases belongs to defaulter
that is 218(46%), 139(29.3%) were
relapse followed by failure 68(14.3%) of
previous anti-tuberculosis treatment. A
study by ICMR shows most of patient
belongs to failure followed by defaulter
then relapse.

Study by Santha et al21 and Johnson
et al22 coincide with our study reporting
defaulter as most common group
affected on basis of previous ATT
taken by patient. We already know
that our study is rural based so that lack of education, low income and
lack of knowledge about the disease
are contributing factors to default.
However, studies by Poulomi et al,10
Ebru et al,19 which shows a high relapse
rate as predominant group.

Conclusion

MDR-TB is an important public health
problem in India. The epidemiological
picture of TB showed that males were
predominant in our study however
female were more affected in younger
age group compared to male. More than
51% of the cases were in productive age
group which affects the socioeconomic
condition of family and society. More
than 2/3 of patients were from lower
socioeconomic group with low BMI.
Therefore improving nutrition and
immunity can play an important
role. Majority of our patients were
from rural area i.e. 61%. 19.2% cases
were addicted to alcohol and 35.4%
cases were addicted to smoking. Comorbidities
like COPD and Diabetes
were seen in our study which were
statistically significant and had impact
on the treatment outcome of results.
6.8% of the cases had history of contact
to cases of tuberculosis so all the contact
must be screened up. Significant delay
in initiation of MDR-TB regimen from
date of DST was seen in 24.3% cases
which is matter of concern Most of the
patients had taken ATT from RNTCP in
which Defaulter and relapse was major
contributor of MDR-TB suspect in our
study and patient taking ATT privately
were less. Large number of cases which
resides more than 150 kilometers from
DRTB center initiated the drug after
a gap of more than 19 days from the
date of DST.

Recommendations

Maximum cases of MDR-TB were
in productive age group and the
disease affects the socio economic
status of family, so financial support
can play an important support in the
management of these cases i.e. some
provision for providing them house
hold jobs. Maximum number of cases
had Anemia and lower BMI so nutrition
may be added as integral part of the
programme. Provision of long term
oxygen therapy (LTOT) be considered
incases with poor lung reserve
and respiratory failure. Cases with
unilateral cavity can be considered for
thoracic surgeries. Delay in initiation
of DRTB regimen was seen in large no of cases (24.3%) which leads to spread
of disease and affect the outcome of
disease so active surveillance of cases
is essential. All the close contact of the
patient should be screened for TB as
significant cases (6.8%) had contact
history of TB in family. De-addiction
programme should be introduced in
national programme as large no of cases
in study were addicted to smoking
and alcohol. Identification, effective
management of co-morbidities and
regular monitoring is very important
in the cases which may help in better
outcome of the result.

References

Ministry of Health and Welfare Government of India, Revised
National TB Control Programme, Technical Guidelines for
Tuberculosis Control in India 2016, Central TB Division,
Directorate General of Health Sciences, New Delhi, India
page 1-269.

Atre SR, et al. Risk Factors Associated with MDR-TB in
Mumbai Risk Factors Associated with MDR-TB at the Onset
of Therapy among New Cases Registered with the RNTCP
in Mumbai, India http://www.ijph.in on Saturday, October
10, 2015, IP: 117.210.60.107.